Process for preparing novel N-(piperazinylethyl)-carbamates

ABSTRACT

N-(piperazinylethyl)-carbamates are prepared in good yield by reacting at an elevated temperature an N-hydrocarbylcarbamate with triethylenediamine or an N-hydrocarbylcarbamate, triethylenediamine and an added alkylating agent. The Npiperazinyl derivatives so-formed are useful as catalysts in the manufacture of polyurethanes, in the preparation of acid-soluble and acid-dyeable polyurethanes.

ilited States Patent Abbate et al.

Feb. 4, 1975 PROCESS FOR PREPARING NOVEL N-(PIPERAZINYLETHYL)-CARBAMATESinventors: Franklin W. Abbate; William J.

Farrissey, Jr., both of North Haven,

Conn.

Assignee: The Upjohn Company, Kalamazoo,

Mich.

Filed: Dec. 13, 1972 Appl. No.: 314,611

Related US. Application Data Division of Ser. No. 15,925, March 2, 1970,Pat No. 3,719,680.

US. Cl 260/268 R Int. Cl C07d 51/70 Field of Search e. 260/268 R, 268 T[56] References Cited UNITED STATES PATENTS 3,721,674 3/1973 Abbate etal. 260/268 R Primary ExaminerDonald G. Daus Attorney, Agent, orFirm-Steward & Steward [57] ABSTRACT 10 Claims, N0 Drawings PROCESS FORPREPARING NOVEL N-(PIPERAZINYLETHYL)-CARBAMATES CROSS REFERENCE TORELATED APPLlCATlONS This is a division of application Ser. No. 15,925,filed Mar. 2, 1970, now US. Pat. No. 3,7 l9,680, issued Mar. 6, i973.

BACKGROUND OF THE INVENTION 1. Field of the Invention This inventionrelates to novel N-(piperazinylethyl)- carbamates and to a method fortheir preparation and relates particularly toN-(piperazinylethyl)-carbamates synthesized by reacting at an elevatedtemperature an N-hydrocarbylcarbamate with triethylenediamine or anN-hydrocarbylcarbamate, triethylenediamine and an added alkylatingagent.

2. Description of the Prior Art The only work previously described inthe art in which triethylenediamine has been employed as a reactant togive a piperazine derivative is that of Ross, et al., JACS 85, 3,999(1963) who reacted 2,4-dinitrochlorobenzene with triethylenediamine toform the compound:

SUMMARY OF THE lNVENTlON The present invention comprises novel compoundsof the formula:

wherein R is hydrocarbyl of l to 12 carbon atoms, wherein R, and R areselected from the group consisting of CH straight chain lower alkyl; CHCl-l R wherein R is selected from the-group consisting of CH O, straightchain lower alkoxy and aryloxy of not more than 12 carbon atoms and withthe proviso that when R is CH CH R then R, is the same substituentgroup, and to a process for preparing such novel compounds.

The novel piperazine derivatives of this invention can be utilized ascatalysts in preparing valuable polyurethane products, in thepreparation of .acid-dyeable modified polyesters and for themodification of polyurethanes prepared from a polyester polyol and apolyisocyanate to yield acid-dyeable or acid-soluble polymers.

Throughout this specification the term hydrocarbyl of from 1 to 12carbon atoms" means the monovalent radical resulting when one hydrogenatom is removed from the parent hydrocarbon having the requisite numberof carbon atoms. Illustrative of such groups are (a) alkyl, such asmethyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl; (b) alkenyl, such as vinyl, allyl, butenyl,pentenyl, hexenyl,

octenyl, dodecenyl. etc.; (c) aralkyl. such as benzyl, phenylethyl.phenylpropyl, phenylhexyl, naphthylmethyl. etc.; (d) aryl, such asphenyl, tolyl. xylyl, naphthyl, bis-phenylyl. etc.; (e) alkaryl, such asethylphenyl, isopropylphenyl, ehtylxylyl, methylnaphthyl, etcl; (f)cycloalkyl, such as cyclobutyl, cyclohexyl, cyclooctyl, cyclodecyl,etc.; and (g) cycloalkenyl such as cyclobutenyl, cyclopentenyl,cyclohexenyl, cyclooctenyl, cyclododecenyl, etc., and isomeric forms ofmembers of the above groups. The phrase straight chain lower alkyl" inthis specification means alkyl of from 2 to 8 inclusive carbon atoms, asexemplified by ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, andisomeric forms thereof. The phrase straight chain lower alkoxy as usedherein means straight chain alkoxy of from 2 to 8 inclusive carbon atomsincluding ethoxy, propoxy. butoxy, pentyloxy, hexyloxy, heptyloxy andoctyloxy. The term aryloxy of not more than 12 carbon atoms meansaryloxy such as phenoxy, xyloxy, naphthoxy, ethylphenoxy,n-propylxyloxy, isobutylphenonoxy, etc.

A wide variety of catalysts are employed in the preparation ofpolyurethanes and especially in preparing polyurethane foams by thereaction of polyisocyanates with polyols in the presence of afluorocarbon foaming atent. One of the most important of these catalystsis triethylenediamine which is employed in substantial quantities in theurethane industry in foam preparation as well as in the manufacture ofother urethane products. It has been found that the novelN-(piperazinylethyl)-carbamates of this invention are valuable urethanecataylsts which may be employed as a substitute for a part or all of thetriethylenediamine commonly utilized in the production of polyurethanesby interaction of diisocyanates and polyols or in the production ofpolyureas by interaction of diisocyanates and polyamines. Methods forproducing such polyurethanes and polyureas in the form of film, fibersand foams utilizing the conventionally employed diisocyanates andpolyols together with the novel catalysts of this invention will bereadily apparent to those skilled in the art. Conventional proceduresfor the synthesis of such polyurethanes are described by Saunders, etal., Polyurethanes, Chemistry and Technology, Part ll, lntersciencePublishers, 1964, pp. 299-451.

Examples of art-recognized polyols which can be employed alone, or asmixtures, in preparing polyurethanes include the following:

1. aliphatic diols, such as ethylene glycol, 1,2- propylene glycol,1,4-butanediol, 1,2-hexanediol, 1,5- pentanediol, 1,2-hexanediol, etc.;

2. aliphatic triols, such as trimethylolmethane, trimethylolethane, l,2,3-hexanetriol, 1,1,1- trimethylolhexane, etc.;

3. aliphatic tetrols, such as erythritol, pentaearythritol, etc.;

4. aliphatic pentols, such as arabitol, xylitol, etc.;

5. aliphatic hexols, such as mannitol, sorbitol, dipentaerythritol,etc.;

6. aniline-alkylene oxide dol adducts; and adducts prepared by reactingany of the above-named compounds l through (5) above with one or moremolar proportions of ethylene oxide, propylene oxide, 1,2- butyleneoxide, or mixtures thereof.

Any of the prior art polyisocyanates can be used as reactants inpreparing polyurethane products when uti lizing the novel products ofthis invention as catalysts, e.g., 2,4-tolylene diisocyanate,2,6-tolylene diisocya- 3 nate, 4,4-diphenylmethane diisocyanate,dianisidine diisocyanate, tolidine diisocyanate, hexamethylenediisocyanate, m-xylyene diisocyanate, 1,5-naphthalene diisocyanate, andother diand higher polyisocyanates such as those listed in the table ofSiefken, Ann. 562, 122-135 (1949). Preferred polyisocyanates, however,are products obtained by phosgenation of mixtures of methylene-bridgedpolyphenyl polyamines obtained by the interaction of formaldehyde,hydrochloric acid, and primary aromatic amines, for example, aniline,ochloroaniline, o-toluidine, or mixtures thereof. Such polyisocyanatesare known in the art, e.g., U.S. Pat. Nos. 2,683,730; 2,950,263; and3,012,008; Canadian Pat. No. 655,495; and German specification No.1,131,877.

In preparing polyurethane products employing the novelN-(piperazinylethyl)-carbamates of this invention as catalysts, or as apart of the catlyst mixture, by reaction of any of the polyisocyanatesconventionally employed in the art with the available polyols, blowingagents, surfactants, cell-openers and the like adjuvants commonlyemployed for the production of polyurethane products may be used. Ifdesired, special polyols such as the phosphorus-containing polyols canbe incorporated in the polyurethane reaction mixture in order to impartfire retardent properties to the resulting foam. Examples of suchphosphorus-containing polyols are the tris polypropylene glycolphosphates produced by interaction of phosphoric and propylene oxide as,for example, described in U.S. Pat. Nos. 2,372,244 and 3,094,549.

DETAILED DESCRIPTION OF THE lNVENTlON 1t-Ni J---R1 n 0 l cmcInN N-R11t-N -O1[ wherein R, has the same meaning as hereinbefore defined.

Process (b) where the N-hydrocarbylcarbamate, triethylenediamine and anadded alkylating agent are reacted together can be illustrativelyrepresented as follows:

wherein R, has the same meaning as previously defined, R is selectedfrom the group consisting of CH straight chain lower alkyl, CH O andstraight chain lower alkoxy. R5 is selected from the group consisting ofCH and straight chain lower alkyl and with the proviso that when R is CHor straight chain lower alkyl then R5 is CH;, and when R, is CH -,O orstraight chain lower alkoxy, the alkyl group thereof has the same numberof carbon atoms as Rs.

In conducting process (a) or (b) ofthis invention, theN-hydrocarbylcarbamate employed asa starting material is preferablyreacted with triethylenediamine in the presence of an inert organicsolvent. The inert organic solvent can be any organic solvent which isinert under the conditions of the reaction, e.g., does not enter intoreaction with any of the reactants employed or in any way interfer withthe progress. of the reaction. Suitable inert organic solvents includebenzene, toluene, xylene, naphthalene, decalin, chlorobenzene,odichlorobenzene, bromobenzene, etc.

Advantageously, processes (a) and (b) .are conducted at a temperatureranging from about to about 300C. and preferably at a temperature withinthe range of about to about 200C. Approximately stoichiometricquantities of the reactants are generally employed in processes (a) and(b) although, if desired, an excess of the carbamate can be utilized.The progress of the conversion of the N-hydrocarbylcarbamate to thedesired piperazine derivative can be followed by any of the appropriateanalytical techniques such as infrared spectrographic analysis, etc. Thedesired N-(piperazinylethyl)-carbamate can be isolated from the reactionmixture of process (a) or (b) by conventional procedures in organicchemical operations such as by extraction, distillation, precicpitationas the hydrochloric acid salt, etc.

The N-hydrocarbylcarbamates utilized as starting materials-in processes(a) and (b) are for the most part known compounds which can be preparedby methods conventional in the art for the preparation of N- substitutedcarbamates. A particularly convenient method involves the reaction ofthe appropriate chloroformate and appropriate hydrocarbylamine; see, forexample, H. von Pechmann, Ber, 28, 855 (1895) for a description of thepreparation of ethyl N- methylcarbamate from methylamine and ethylchloroformate as representative of the conditions required in preparingthis series of compounds. Another method for the preparation ofN-substituted carbamates involves the reaction of the correspondingN-substituted carbamyl halide with the appropriate alcohol for example,using the procedure described by Gattermann, Annalen 244,30 1888) forthe reaction of carbamyl chloride itself with alcohols.

N-substituted carbamates can also be otained by the alkylation ofolefins with urethane (ethyl carbamate) as described by Mueller andMerten, Ber, 98, 1097 (1965) and by condensation of aldehydes with alkylcarbamates as described, for instance, by Bischoff, Ber, 7, 628 (1874).

Various embodiments of this invention are illustrated in the followingexamples which are to be considered not limitative:

EXAMPLE 1 Methyl N-phenyl-N-methylpiperazinylethylcarbamate A total of15.2 g. of methyl N-phenyl carbamate. 5.6 g. of triethylenediamine andml. of methyl carbonate were added with mixing at room temperature to100 ml. of chlorobenzene. The mixture was heated over a period of aboutminutes to refluxing temperature and the refluxing operation wascontinued over a period of about 5 hours.

Following dilution of the reaction mixture with ether, it was extractedwith four portions of hydrochloric acid (5 percent by volume) andfinally with water. In the next step the resulting aqueous acid layerwas washed with two portions of ether. The organic layers were combined,washed with a saturated salt solution and finally dried over magnesiumsulfate and after evaporation of the ether, residue containing theunreacted starting carbamate weighing 10.2 grams was obtained.

The acid aqueous layer was made basic through the addition of sodiumhydroxide (10 percent by volume), saturated with sodium chloride andthen extracted with five portions of ether. After the ether phase hadbeen washed to neutrality with a saturated salt solution, it was driedover magnesium sulfate and on evaporation there was recovered 11.3 g.(82 percent ofthe theoretical yield) of the compound having the formula:

boiling point 156158C. at 0.5 mm. Hg, which was identified by infraredspectrographic nuclear magnetic reasonance analyses as well as byelemental analysis.

Analysis Calcd for C 5H O N C,65.95; H,8.36; N,15.15. Found: C,65.l4;H.842; N,15.22.

EXAMPLE ll Butyl N-phenyl-N-butylpiperazinylethercarbamate To 35 ml. ofbutyl carbamate there was added with mixing at room temperature 38.74 g.of butyl N- phenylcarbamate, and 22.48 g. of triethylenediamine afterwhich the reaction mixture was heated with mixing for hours at 150C. Inthe next step, the resulting mixture was diluted with ether and thenworked up into basic and neutral fractions utilizing the generalprocedure employed in Example 1.

From the basic phase there was recovered a total of 19.68 g. (50.8percent of the theoretical yield) of the compound having the formula:

boiling point 185187C. at 0.4 mm. Hg, which was identified by infraredspectrographic anaylsis as well as by elemental analysis.

Analysis-Calcd. for c iiao mz C.69.77; H,9.76; N,l1.62. Found: C,69.39;H,9.70; N,11.81.

EXAMPLE lll Butyl N-phenyl-N-methylpiperazinylethylcarbamate In thisexample 38.6 g. 'of butyl N-phenylcarbamate, 13.0 g. of methylhexanoate. and 12.4 g. of triethylenediamine were heated with mixing at150C. for 24 hours. The reaction mixture was cooled. diluted with etherand water and then filtered. The resulting etheral portion was washedwith l N hydrochloric acid until acidic while the combined aqueous phasewas washed with ether, made basic with sodium hydroxide 10 percent byvolume) and finally continuously extracted with ether. After the etheralphase had been dried over magnesium sulfate, there was obtained onevaporation of the ether approximately 10 g. of a basic mixture which ondistillation yielded 5.5 g. (16 percent of the theoretical yield) of thecompound of the formula:

The above product was identified by infrared spectrographic and nuclearmagnetic resonance analyses.

EXAMPLE IV A total of 38.6 g. of butyl N-phenylcarbamate, 13.0 g. ofmethyl hexanoate, and 12.4 g. of triethylencdiamine were added withmixing to 20 m1. of butyl carbonate. The reaction mixture was heated at150C. with mixing for 4 hours. After the reaction mixture had cooled, itwas diluted with ether and the etheral phase extracted with 1 Nhydrochloric acid. Employing the general procedure of Example 1 therewas recovered from the basic phase 10.1 g. (32 percent of thetheoretical yield) of the compound of the formula:

boiling point l181C. at 0.7 mm. Hg. The compound was further identifiedby infrared, nuclear magnetic resonance and vapor phase chromatographyanalyses.

Analysis Calcd. for C H N O z C,67.67; H,9.15; and N,l3.l6. Found:C,67.70: H,9.()4;N,13.5().

EXAMPLE V octyl N-pentenyl-N-methylpiperazinylethylcarbamate,

ethyl N-naphthyl-N-methylpiperazinylethylcarbamate,

butyl N-ethylxylyl-N-methylpiperazinylethylcarbamate,

. propyl N-cyclohexyl-N-methylpiperazinylethylcarbamate, methylN-benzyl-N-methylpiperazinylethylcarbamate, and heptylN-cyclobutenyl-N-methylpiperazinylethylcarbamate, respectively.

EXAMPLE VI A total of 7.8 g. of methyl N-phenylcarbamate and 3.0 g. oftriethylenediamine were refluxed in I ml. of chlorobenzene for 6 hours.After the reaction mixture had been filtered, it was worked up intobasic and neutral fractions using the general procedure of Example I.The basic fraction gave in excess of 50 percent of the theoretical yieldof a product which was shown to be identical to the compound obtained inExample I (i.e., methyl N-phenyl-N-methylpiperazinylethyl carbamate) byinfrared-spectrographic and vapor phase chromatographic analyses.

EXAMPLE Vll Using the procedure of Example Vl but replacing methylN-phenylcarbamate with phenoxyethyl N- phenylcarbamate there wasobtained in good yield phenoxyethylN-phenyl-N-phenoxyethylpiperazinylethylcarbamate.

EXAMPLE VIII Employing the procedure of Example I but substituting ethylcarbonate, n-propyl carbonate and hexyl carbonate for methyl carbonatethere are obtained in comparable yield:

methyl-N-phenyl-N-ethylpiperazinylethylcarbamatemethyl-N-phenyl-N-n-propylpiperazinylethylcarbamatemethyl-N-phenyl-N-hexylpiperazinylethylcarbamate.

Highly useful polyurethane foams can be prepared in which the novelN-(piperazinylethyl)-carbamates of this invention are employed ascatalysts. The preparation of a typical foam product is set forth in thefollowing preparation:

Using a mechanical blender, 100 parts by weight of polyol of equivalentweight l33 which is a blend of (i) an adduct of propylene oxide and amethylene bridged polyphenyl polyamine mixture obtained by acidcondensation of aniline and formaldehyde and (ii) a glycerol-propyleneoxide adduct, 2 parts by weight of a water-soluble silicone-glycolcopolymer cell control agent and foam stabilizer, and 3.2 parts byweight methyl N-phenyl-N-methylpiperazinylethylcarbamate are mixedtogether after which 32 parts by weight of a blowing agent, which isstabilized trichlorofluoromethane, is added. To the resulting mixture isadded, as rapidly as possible, 112 parts by weight of polymethylenepolyphenyl isocyanate of equivalent weight 1 l3 (PAPI). The mixturethus-obtained is stirred with a high speed stirrer for approximately 30seconds and then is poured into an open mold (7 X 7 X 12 inch). Theresulting foam, which is allowed to rise freely, is cured at roomtemperature (about to C.) for 7 days and afterwards subjected tophysical testing. A polyurethane foam suitable for a wide variety ofcommercial application, such as in the preparation of packagingcontainers, structural panels, etc. is obtained.

What is claimed is: 1. A process for preparation of a compound of theformula:

0 RN(H]O-R1 wherein R is a hydrocarbon group selected from the groupconsisting of alkenyl having 2 to 12 carbon atoms, and cycloalkyl andcycloalkenyl having 4 to 8 carbon atoms, and aryl and aralkyl andalkaryl having 7 to 12 total carbon atoms: R; is selected from the groupconsisting of CH and straight chain lower alkyl of from 2 to 8 inclusivecarbon atoms; CH CH R wherein R is selected from the group consisting ofCH O and straight chain lower alkoxy of from 2 to 8 inclusive carbonatoms, and aryloxy of from 6 to 12 carbon atoms and with the provisothat when R5 is CH CH R then R is the same substituent group; whichcomprises the step of reacting a carbamate of the formula:

wherein R and R have the same meaning as previously defined, withtriethylenediamine and an alkylating agent of the formula:

R COOR5,

wherein R is selected from the group consisting of CH and straight chainlower alkyl of from 2 to 8 inclusive carbon atoms, CH O and straightchain lower alkoxy of from 2 to 8 inclusive carbon atoms, R is selectedfrom the group consisting of CH and straight chain lower alkyl of from 2to 8 inclusive carbon atoms; and with the proviso that when R. is CH, orstraight chain lower alkyl, then R5 is CH and when R, is CH -,O orstraight chain lower alkoxy, the alkyl group thereof has the same numberof carbon atoms as R5 aryl being selected from the group of phenyl andnaphthyl; said reaction being conducted in the presence of an inertorganic solvent which is a liquid at room temperature.

2. The process of claim 1 wherein the reaction is conducted at atemperature of from about to about 3. The process of claim 1 wherein Ris aryl.

4. The process of claim I wherein R is phenyl, R is CH3, R4 is CHsO, andR5 is CH3.

5. The process of claim 1 wherein R is phenyl, R, is CH3(CH2)3, R4 isand R5 is CH3(CH2)3.

6. The process of claim 1 wherein R is phenyl, R is CH (CH R isCH;,(CH)40, and R; is CH;,.

7. A process for preparing a compound of the formula:

wherein R is a hydrocarbon group selected from the group consisting ofalkenyl having 2 to l2 carbon atoms and cycloalkyl and cycloalkenylhaving 4 to 8 wherein R and R have the same meaning as previously carbonatoms, R, is selected from the group consisting d fi d wi h i h l di iof CH and straight chain lower alkyl of from 2 to 8 inelusive carbonatoms and CHZCH2 R3, wherein R3 is 8. The process ofclaim 7 wherein thereaction is conselected from the group consisting of CH3O, traightdLlCtfid at a temperature Of about 80 to about 300C. chain lower alkoxyof from 2 to 8 inclusive carbon atoms and aryloxy of 6 or 10 carbonatoms: which comprises the step of reacting a carbamate of the formula:

9. The process of claim 7 wherein the reaction is conducted in thepresence of an inert organic solvent.

10. The process of claim 7 wherein R is phenyl and H 0 l() R, is CH3,864, 345 Dated February 4, 1975 Patent No.

Inventor) Franklin W. Abbate and William J. Farrissey, Jr.

It is certified that error appears in the above-identified patent andthat said Letters Patent are hereby corrected as shown below:

Column 2, Line 5: Should read:

ethylxylyl, methylehtylxylyl, methylnaphthyl, etc.;

naphthyl, etcl;

Should read:

Column 3, Lines 13 and 14:

Canadian Pat.No. 655,495; Canadian Patent No. 665,495;

Column 5, Line 41: Should read:

Butyl N--phenylN-butylpiperazinylethercarbamate BucylNphenyl-N-butylpiperazinylethylcarbamate Column 8, Claim 6, Line 57:Should read:

CH3 (CI-I o, CH3 (CH2 ),0,

Signed and sealed this 29th day of April 1975.

(SEAL) Attest:

RUTH C. MASON Attesting Officer C. MARSHALL DANN Commissioner of Patentsand Trademarks Q wo-wso (10-69) USCOMM-DC 6O376-P69 U.S. GOVERNMENTPRINTING OFFICE I969 0-356-3Sl

1. A PROCESS FOR PREPARATION OF A COMPOUND OF THE FORMULA:
 2. Theprocess of claim 1 wherein the reaction is conducted at a temperature offrom about 80* to about 300*C.
 3. The process of claim 1 wherein R isaryl.
 4. The process of claim 1 wherein R is phenyl, R1 is CH3, R4 isCH3O, and R5 is CH3.
 5. The process of claim 1 wherein R is phenyl, R1is CH3(CH2)3, R4 is CH3(CH2)3O and R5 is CH3(CH2)3.
 6. The process ofclaim 1 wherein R is phenyl, R1 is CH3(CH2)3, R4 is CH3(CH2)4o, and R5is CH3.
 7. A process for preparing a compound of the formula:
 8. Theprocess of claim 7 wherein the reaction is conducted at a temperature ofabout 80* to about 300*C.
 9. The process of claim 7 wherein the reactionis conducted in the presence of an inert organic solvent.
 10. Theprocess of claim 7 wherein R is phenyl and R1 is CH3.